ID | 114573 |
著者 |
Miura, Kaori
Prefectural University of Hiroshima
Haraguchi, Misaki
Prefectural University of Hiroshima
Ito, Hideyuki
Okayama Prefectural University
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キーワード | ascorbic acid
stable ascorbic acid derivatives
acyl ascorbic acid
antitumor activity
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資料タイプ |
学術雑誌論文
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抄録 | Intravenous administration of high-dose ascorbic acid (AA) has been reported as a treatment for cancer patients. However, cancer patients with renal failure cannot receive this therapy because high-dose AA infusion can have side effects. To solve this problem, we evaluated the antitumor activity of a lipophilic stable AA derivative, 2-O-α-D-glucopyranosyl-6-O-(2-pentylheptanoyl)-L-ascorbic acid (6-bOcta-AA-2G). Intravenous administration of 6-bOcta-AA-2G suppressed tumor growth in colon-26 tumor-bearing mice more strongly than did AA, even at 1/10 of the molar amount of AA. Experiments on the biodistribution and clearance of 6-bOcta-AA-2G and its metabolites in tumor-bearing mice showed that 6-bOcta-AA-2G was hydrolyzed to 6-O-(2-propylpentanoyl)-L-ascorbic acid (6-bOcta-AA) slowly to yield AA, and the results suggested that this characteristic metabolic pattern is responsible for making the antitumor activity of 6-bOcta-AA-2G stronger than that of AA and that the active form of 6-bOcta-AA-2G showing antitumor activity is 6-bOcta-AA. In in vitro experiments, the oxidized form of 6-bOcta-AA as well as 6-bOcta-AA showed significant cytotoxicity, while the oxidized forms of ascorbic acid showed no cytotoxicity at all, suggesting that the antitumor activity mechanism of 6-bOcta-AA-2G is different from that of AA and that the antitumor activity is due to the reduced and oxidized form of 6-bOcta-AA. The findings suggest that 6-bOcta-AA-2G is a potent candidate as an alternative drug to intravenous high-dose AA.
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掲載誌名 |
International Journal of Molecular Sciences
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ISSN | 14220067
16616596
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cat書誌ID | AA12038549
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出版者 | MDPI
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巻 | 19
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号 | 2
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開始ページ | 535
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発行日 | 2018-02-10
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権利情報 | © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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出版社版DOI | |
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言語 |
eng
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著者版フラグ |
出版社版
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部局 |
生物資源系
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